BR112020001850A2 - antimicrobial mixture, composition, cosmetic treatment process, process to preserve a composition and use of an antimicrobial mixture - Google Patents

Abstract

The invention relates to an antimicrobial mixture containing 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and an ammonium compound chosen from a C20 to C24 trimethylammonium grease salt and a salt of (C8-C28) alkyldimethylbenzylammonium, and also to a cosmetic composition containing such a mixture. Use in the care, makeup and cleaning of keratin materials.

Description

"ANTIMICROBIAL MIXTURE, COMPOSITION, COSMETIC TREATMENT PROCESS, PROCESS TO MAINTAIN A COMPOSITION AND USE OF AN ANTIMICROBIAL MIXTURE"

[0001] An object of the present invention is an antimicrobial mixture containing 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and a particular ammonium compound, and also subsequently a cosmetic composition containing such a mixture.

[0002] 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one (ketone compound) is a useful substance as a preservative agent for cosmetic compositions, to protect the compositions against microbial contamination, as described in the application for patent in WO 2011/039445.

[0003] However, it is desirable to be able to incorporate said ketone compound in reduced concentration into the compositions, especially cosmetic or dermatological compositions, while maintaining good performance of antimicrobial conservation. Combinations of the ketone compound with other preservative agents that have good antimicrobial efficacy are thus sought for this purpose.

[0004] The inventors unexpectedly found that the combination of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one with an ammonium compound chosen from a grease chain alkyl trimethylammonium salt and an alkyldimethylbenzylammonium salt, as defined below, in particular, beenyltrimethylammonium chloride or an alkyldimethylbenzylammonium chloride, makes it possible to obtain an antimicrobial mixture with synergistic antimicrobial activity, in particular, at least in molds, especially in Aspergillus niger.

[0005] The results of the examples described below show the synergistic antimicrobial activity obtained with the measurements of minimum inhibitory concentration (MIC) performed with various mixtures. Antimicrobial activity is considered synergistic when the antimicrobial mixture allows to obtain a percentage of growth of the strain less than or equal to 25%, or even less than or equal to 20%.

[0006] The combination of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one with a particular fatty acid alkyltrimethylammonium salt, as defined below, in particular, beenyltrimethylammonium chloride, makes it possible to obtain an antimicrobial mixture with synergistic antimicrobial activity, in particular, in molds, especially in Aspergillus niger, in yeasts, in particular in Candida albicans, and in gram-negative bacteria, especially in Pseudomonas aeruginosa.

[0007] The combination of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one with an alkyldimethylammonium salt, as defined below, in particular, an alkyldimethylbenzylammonium chloride, makes it possible to obtain an antimicrobial mixture with synergistic antimicrobial activity , in particular, in molds, especially in Aspergillus niger.

[0008] More precisely, an object of the invention is an antimicrobial mixture which comprises or consists of (or consists of), 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and an ammonium compound chosen from of: i) an alkyltrimethylammonium salt of the formula R-N + (CH3) 3 X- (I) in which R denotes an alkyl group containing 20 to 24 carbon atoms, X - denotes a halide ion, in particular chloride or bromide, or a methosulfate ion; ii) an alkyldimethylbenzylammonium salt of the formula (II): C6H5-CH2-N + (CH3) 2R X- (II) in which R denotes an alkyl radical containing 8 to 18 carbon atoms, X- denotes a halide anion like chloride or bromide.

[0009] An objective of the invention is also a composition,

especially, a cosmetic composition comprising, in a physiologically acceptable medium, said mixture described above.

[0010] A further object of the invention is a process for the non-therapeutic cosmetic treatment of keratin materials which comprises applying to the keratin materials a composition as previously described. The process can be a cosmetic process for the care, makeup or cleaning of keratin materials.

[0011] An object of the invention is also a process for preserving a composition that comprises a physiologically acceptable medium, in particular, a cosmetic or dermatological composition, characterized by the fact that it consists of incorporating in said composition an antimicrobial mixture, as previously described.

[0012] An object of the invention is also the use of the antimicrobial mixture previously described to preserve a composition that comprises a physiologically acceptable medium.

[0013] 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one is a compound of the formula:

HO THE THE

[0014] According to a first embodiment, an objective of the invention is an antimicrobial mixture which comprises or consists of (or consists of), 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and a salt of alkyltrimethylammonium of the formula R-N + (CH3) 3 X- (I) where R denotes an alkyl group containing 20 to 24 carbon atoms, X - denotes a halide ion, in particular chloride or bromide, or an ion of methosulfate.

[0015] For the alkyl trimethylammonium salt of formula (I) described above, R is preferably a behenylene group.

[0016] Preferably, X- is a chloride anion.

[0017] Advantageously, the alkyltrimethylammonium (I) salt is beenyltrimethylammonium chloride (INCI name: beentrimonium chloride).

[0018] beenyltrimethylammonium chloride can be used as a mixture at 79% by weight with 18% isopropyl alcohol and 3% water sold under the name Genamin KDMF by the company Clariant.

[0019] Advantageously, 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and the trimethylammonium salt (I) are present in said mixture in a content so that the weight ratio of 4- (3- ethoxy-4-hydroxyphenyl) butan-2-one / salt (I) (preferably beenyltrimethylammonium chloride) is in the range of 0.08 to 80, preferably from 0.45 to 70 and preferably from 1 , 5 to 50.

[0020] The antimicrobial mixture, according to the invention, has synergistic antimicrobial activity, in particular, in molds, especially in Aspergillus niger, in yeasts, in particular, in Candida albicans, and in gram-negative bacteria, in particular, in Pseudomonas aeruginosa.

[0021] Preferably, the antimicrobial mixture according to the invention contains beenyltrimethylammonium chloride.

[0022] The antimicrobial mixture can have a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / salt (I) (preferably beenyltrimethylammonium chloride) which is in the range of 10 to 60, preferably in the range of 10 to 55 and, preferably, in the range of 15 to 40, and even better in the range of 20 to 30. Such mixture has good antimicrobial activity in yeasts, especially in Candida albicans.

[0023] The antimicrobial mixture can have a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / salt (I) (preferably beenyltrimethylammonium chloride) which is in the range of 0, 08 to 5, preferably in the range of 0.45 to 4.5, preferably in the range of 0.45 to 3, even better from 0.4 to 2.5 and preferably in the range of 1.5 to 3. This mixture has good antimicrobial activity in molds, especially in Aspergillus niger.

[0024] The antimicrobial mixture can have a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / salt (I) (preferably beenyltrimethylammonium chloride) which is in the range of 3 to 80, preferably in the range of 3 to 70, preferably in the range of 3 to 50, and even better in the range of 3 to 45.

Such a mixture has good antimicrobial activity in gram-negative bacteria, especially in Pseudomonas aeruginosa.

[0025] According to a second embodiment, an objective of the invention is an antimicrobial mixture that comprises or consists of (or consists of), 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and a salt of alkylldimethylbenzylammonium of the formula (II): C6H5-CH2-N + (CH3) 2R X- (II) where R denotes an alkyl radical containing 8 to 18 carbon atoms, X- denotes a halide anion such as chloride or bromide.

[0026] For the alkyldimethylbenzylammonium salt of formula (II) described above, R is preferably an alkyl group comprising 10 to 16 carbon atoms and, preferably, 12 to 14 carbon atoms.

[0027] Preferably, X- is a chloride anion.

[0028] An alkyldimethylbenzylammonium chloride (INCI name: benzalkonium chloride) is preferably used.

[0029] Advantageously, the alkyldimethylbenzylammonium salt is a mixture of lauryldimethylbenzylammonium chloride (compound IIa; R = C12 alkyl) and myristyldimethylbenzylammonium chloride (compound IIb; R = C14 alkyl).

[0030] Use is preferably made of a mixture chosen from: a) a mixture comprising 60% to 80% compound IIa and 20% to 40% compound IIb b) a mixture comprising 65 % to 75% compound IIa and 25% to 35% compound IIb c) a mixture comprising 68% to 72% compound IIa and 28% to 32% compound IIb d) a mixture comprising 70% compound IIa and 30% compound IIb.

[0031] The percentages indicated are molar percentages in relation to the total number of moles of said mixture.

[0032] Advantageously, 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and the alkyldimethylbenzylammonium (II) salt are present in said mixture in contents so that the weight ratio of 4- (3-ethoxy -4-hydroxyphenyl) butan-2-one / salt (II) (preferably an alkyldimethylbenzylammonium chloride) is in the range of 5 to 120, preferably of 5 to 100, preferably of 5 to 85, more preferably , from 30 to 85 and, in particular, from 35 to 85.

[0033] The antimicrobial mixture, according to the invention, has synergistic antimicrobial activity, in particular in molds, especially in Aspergillus niger.

[0034] Preferably, the antimicrobial mixture according to the invention contains an alkyldimethylbenzylammonium chloride.

[0035] An object of the invention is also a composition that comprises, in a physiologically acceptable medium, the antimicrobial mixture described above.

[0036] The term "physiologically acceptable medium" means a medium that is compatible with human keratin materials, such as skin, scalp, hair and nails. Said medium may comprise one or more additional ingredients other than the ketone compound and the ammonium compound described above.

[0037] The compound 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one can be present in the composition according to the invention in an amount ranging from 0.01% to 5% by weight in relation to the total weight of the composition, preferably in the range of 0.01% to 3% by weight, preferably in the range of 0.01% to 2.5% by weight and, more preferably, in the range of 0.01 % to 2% by weight.

[0038] The composition may comprise at least one additional ingredient chosen from water, oils, polyols containing from 2 to 10 carbon atoms, gelling agents, surfactants, film-forming polymers, dyes, fragrances, fillers, protective agents against UV, plant extracts, active cosmetic and dermatological agents and salts.

[0039] The composition according to the invention can comprise an aqueous phase.

[0040] The composition can comprise water, which can be present in a content in the range of 5% to 90% by weight in relation to the total weight of the composition and, preferably, in the range of 35% to 75% by weight.

[0041] The composition may also comprise a polyol that is miscible in water at room temperature (25 ° C), specially chosen from polyols that contain especially 2 to 10 carbon atoms, preferably containing 2 to 6 atoms carbon, such as glycerol, propylene glycol, 1,3-propanediol, butylene glycol, pentylene glycol, hexylene glycol, dipropylene glycol, diethylene glycol or diglycerol. Advantageously, the composition according to the invention comprises 1,3-propanediol, especially in a range ranging from 0.1% to 20% by weight, preferably in the range of 0.1% to 10% by weight. weight and, preferably, in the range of 0.5% to 5% by weight, in relation to the total weight of the composition.

[0042] The compositions according to the invention can be in the form of oil in water (O / W) emulsions, water in oil (W / O) emulsions or multiple emulsions (triple: A / O / W or O / W / O), oily solutions, oily gels, aqueous solutions, aqueous gels, solid compositions. These compositions are prepared according to the usual methods.

[0043] The compositions according to the invention can be more or less fluid and can have the appearance of a white or colored cream, an ointment, a milk, a lotion, a serum, a paste or a foam. These can optionally be applied to the skin as an aerosol. These can also be in solid form, for example in the form of a stick or a compact powder.

[0044] The composition according to the invention can be especially in the form of: - a makeup product, especially to make up the skin of the face, body, lips or eyelashes; - an aftershave gel or lotion; a shaving product; - a deodorant (stick, with a ball or aerosol applicator); - a hair removal cream; - a body hygiene composition, such as a shower gel or a shampoo; - a pharmaceutical composition; - a solid composition, such as a soap or a cleaning bar; an aerosol composition which also comprises a pressurized propellant; - a styling lotion, a hair styling cream or gel, a dyeing composition, a permanent waving composition,

a lotion or gel to fight hair loss or a hair conditioner; - a composition to care for or cleanse the skin.

[0045] An object of the invention is also a process for preparing a composition, especially a cosmetic or dermatological composition, which comprises a step of mixing 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one, the ammonium compound previously described and one or more additional ingredients, especially cosmetic or dermatological ingredients, such as those previously described.

[0046] The invention is illustrated in more detail in the example that follows. The quantities of the ingredients are expressed as percentages by weight.

EXAMPLE 1: DETERMINATION OF SYNERGIC ANTIMICROBIAL ACTIVITY AS MIC

[0047] The demonstration of an effect of synergistic antimicrobial activity with a mixture of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one (called substance A) and the ammonium compound (called substance B) is calculated by calculating the synergy index (or FIC index).

FORMULATION Index FIC = (MICa with B / MICa) + (MICb with A / MICb) with: - MICa with B: minimum concentration of product A in the combination A + B that makes it possible to obtain an inhibitory effect; - MICb with A: minimum concentration of product B in the combination A + B, which makes it possible to obtain the inhibitory effect; - MICa: minimum inhibitory concentration of product A alone; - MICb: minimum inhibitory concentration of product B alone.

[0048] This formula was first described in the article by F.C.Kull, P.C. Eisman, H.D. Sylwestrowka, and R.L.Mayer, Applied Microbiology

9: 538 to 541, 1961.

[0049] For each compound tested alone, MIC is considered as the first concentration that makes it possible to obtain a percentage of microbial growth less than or equal to 25%.

[0050] With respect to the tested combinations, MICa with b and MICb with a are the respective concentrations of A and B in the combinations that make it possible to obtain a percentage of microbial growth less than or equal to 25%.

INTERPRETATION OF THE FIC INDEX:

[0051] When the value of the FIC index is less than or equal to 1, the combination of test compounds is considered to have a synergistic effect.

[0052] The results obtained are summarized in the following Tables.

[0053] The combination of compounds A and B has been tested on the following strains or on a portion of these strains: Aspergillus niger, Candida albicans, Pseudomonas aeruginosa.

[0054] The microbial strain Aspergillus niger ATCC 6275 and a liquid culture medium of double concentration Sabouraud broth supplemented with polyoxyethylene sorbitan monopalmitate (20 OE) (Tween 40 next to Croda) and Phytagel © BioReagent.

[0055] The microbial strain Candida albicans ATCC 10231 and a liquid culture medium of Sabouraud broth of double concentration were used.

[0056] The microbial strain Pseudomonas aeruginosa ATCC 9027 and a liquid culture medium of double concentration nutrient broth were used.

[0057] A 96-well microplate and an incubation time at 32.5 ° C are used.

[0058] The microplate incubation time is: - from 24 hours to 48 hours aerobically for Aspergillus niger; - 18 to 24 hours aerobically for Candida albicans and Pseudomonas aeruginosa.

TESTS

[0059] For each compound: A = 4- (3-ethoxy-4-hydroxyphenyl) -2-butanone compound B = beenyltrimethylammonium chloride (as a 79% by weight mixture with 18% isopropyl alcohol and 3% water sold under the name Genamin KDMF by the company Clariant *) * The isopropyl alcohol present is considered to have no influence on the MIC results obtained.

[0060] A stock solution of 10% (weight / volume) was prepared by mixing 1 g of the compound in 9 ml of 1% aqueous solution of agar. Successive dilutions were made with the 1% agar solution.

COMPOUNDS TESTS A AND B ALONE

[0061] 50 µl of each of the daughter solutions obtained that contain compound A or B are added to the microplate wells. 100 µl of Sabouraud liquid nutrient broth inoculated with the Aspergillus niger strain and 50 µl of 1% aqueous solution of agar are also added to it.

COMPOUNDS TESTS A AND B AS A MIXTURE

[0062] 50 µl of each of the obtained daughter solutions containing compound A and 50 µl of each of the obtained daughter solutions containing compound B are added to the microplate wells. 100 µl of Sabouraud liquid nutritious broth inoculated in double concentration with the Aspergillus niger strain are also added to it.

MICROBIAL GROWTH CONTROL

[0063] A positive microbial growth control was also prepared. The positive microbial growth control corresponds to a mixture of 100 µl of a 1% aqueous solution of agar with 100 µl of liquid Sabouraud nutrient broth inoculated in double concentration with the Aspergillus niger strain in the absence of compounds A and B.

ABSORBANCE CONTROL OF ISOLATED A AND B COMPOUNDS

[0064] An absorbance control was performed in parallel only on compounds A and B. This control corresponds to 100 µl of double-concentration sterile Sabouraud liquid nutrient broth + 100 µl of double-concentration compound A or B.

[0065] In the three cases (absorbance control, growth control and test), the final volume present in each well of the microplate is 200 µl.

[0066] In both cases (test and control), the inoculum represents the concentration of the Aspergillus niger strain present in the final volume of the wells (200 µl) and is between 2 and 6 × 105 cfu / ml of Aspergillus niger.

[0067] The minimum inhibitory concentration (MIC) of each compound A and B alone and in combination was determined in a known manner by measuring optical density at a wavelength of 620 nm.

[0068] The test as described above (tests, absorbance control and growth control) was performed again to test the combination A + B in the strains Candida albicans and Pseudomonas aeruginosa.

[0069] The following results were obtained with B1 = beenyltrimethylammonium chloride (as a mixture of 79% by weight with 18% isopropyl alcohol and 3% water sold under the name Genamin KDMF by the company Clariant *) * the isopropyl alcohol present has no influence on the MIC results obtained.

Candida albicans Concentrations 0A 0.025 A 0.05 A 0.1 A 0.2 A tested (% by weight) 0 B1 73 73 49 9 0.002 B1 50 13 8 14 1 (FIC 0.63) (FIC 0.75) ( FIC 1) 0.00395 B1 1 0 0 1 1% MIC of% MIC of MIC of each compound as FIC Index Ratio A / B1 A alone B1 alone a mixture% A% B1 0.2 0.00395 0.025 0.002 0.63 12.5

[0070] The results obtained show synergistic inhibitory activity for the mixtures: i) 0.025% A and 0.002% B1, that is, ratio A / B1 = 12.5 ii) 0.05% A and 0.002% B1 , that is, ratio A / B1 = 25 iii) 0.1% of A and 0.002% of B1, that is, ratio A / B1 = 50 Aspergillus niger Concentrations 0A 0.025 A 0.05 A 0.1 A 0.2 A 0.4 A tested (% by weight) 0 B1 150 113 112 75 5 0.049 B1 186 138 178 -8 -7 -15 (FIC 0.31) (FIC 0.56) 0.1 B1 155 139 114 18 18 - 7 8 (FIC 0.37) (FIC 0.62) 0.2 B1 78 131 100 15 -21 9 (FIC 0.49) (FIC 0.74) 0.4 B1 34 66 -14 19 -14 -10 (FIC 0.60) (FIC 0.73) (FIC 0.98) 0.79 B1 8 20 26 -35 -20 -50% MIC% MIC of MIC of each compound as FIC Index Ratio A / B1 of B1 alone a mixture alone% A% B1 0.4 0.79 0.1 0.049 0.31 2

[0071] The results obtained show synergistic inhibitory activity for the mixtures:

i) 0.05% of A and 0.4% of B1, that is, ratio A / B1 = 0.125 ii) 0.1% of A and 0.4% of B1, that is, ratio A / B1 = 0 , Iii) 0.1% A and 0.2% B1, that is, ratio A / B1 = 0.5 iv) 0.1% A and 0.1% B1, that is, ratio A / B1 = 1 v) 0.1% of A and 0.049% of B1, that is, ratio A / B1 = 2 vi) 0.2% of A and 0.4% of B1, that is, ratio A / B1 = 0.5 vii) 0.2% A and 0.2% B1, that is, ratio A / B1 = 1 viii) 0.2% A and 0.1% B1, that is, ratio A / B1 = 2 ix) 0.2% of A and 0.049% of B1, that is, ratio A / B1 = 4 Pseudomonas aeruginosa Concentrations 0 A 0.0625 A 0.125 A 0.25 A 0.5 A 1A tested (in % by weight) 0 B1 114 59 65 41 15 0.001975 B1 68 85 64 49 45 49 0.00395 B1 93 65 75 52 51 21 0.0079 B1 36 35 31 25 18 (FIC 0.75) 8 0.0158 B1 30 5 (FIC 0.56) 0 (FIC 0.63) -1 (FIC 0.75) 0 (FIC 1) 40 0.0316 B1 1 -3 -2 0 4 -34% MIC% MIC of MIC of each compound as FIC Index Ratio A / B1 of A B1 alone a mixture alone% A% B1 1 0.0316 0.0625 0.0158 0.56 3.95

[0072] The results obtained show synergistic inhibitory activity for the mixtures: i) 0.0625% of A and 0.0158% of B1, that is, ratio A / B1 = 3.95 ii) 0.125% of A and 0, 0158% B1, that is, A / B1 ratio = 7.91 iii) 0.25% A and 0.0158% B1, that is, A / B1 ratio = 15.82 iv) 0.5% A and 0.0158% B1, that is, ratio A / B1 = 31.64 v) 0.5% A and 0.0079% B1, that is, ratio A / B1 = 63.29

EXAMPLE 2: DETERMINATION OF SYNERGIC ANTIMICROBIAL ACTIVITY AS MIC

[0073] The demonstration of an effect of synergistic antimicrobial activity with a mixture of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one (called substance A) and (C12-C14) alkylldimethylbenzylammonium chloride (called substance B2) is performed according to the protocol described in Example 1, using the Aspergillus niger strain.

[0074] B2 = (C12-C14) alkylldimethylbenzylammonium chloride = mixture of 70 mol% of benzildimethyldodecylammonium chloride and 30% mol of benzyldimethyltetradecylammonium chloride (sold under the name benzalkonium chloride product n ° 12060 by the company Sigma-Aldrich )

[0075] The following results were obtained: Aspergillus niger Concentrations 0A 0.025 A 0.05 A 0.1 A 0.2 A 0.4 A tested (% by weight) 0 B2 212 92 68 29 17 0.0025 B2 194 159 92 2 2 1 (FIC 0.5) (FIC 0.75) 0.005 B2 194 164 2 2 2 2 (FIC 0.63) (FIC 0.75) (FIC 1) 0.01 B2 2 2 2 2 2 2 % MIC% MIC MIC of each compound FIC index A / B2 ratio of A to B2 as a mixture alone alone% of A% of B2 0.4 0.01 0.05 0.005 0.63 10

[0076] The results obtained show synergistic inhibitory activity for the mixtures: i) 0.05% of A and 0.005% of B2, that is, ratio A / B2 = 10 ii) 0.1% of A and 0.005% of B2 , that is, ratio A / B2 = 20 iii) 0.1% of A and 0.0025% of B2, that is, ratio A / B2 = 40 iv) 0.2% of A and 0.005% of B2, that is that is, ratio A / B2 = 40 v) 0.2% of A and 0.0025% of B2, that is, ratio A / B2 = 80.

Claims (20)

1. ANTIMICROBIAL MIXTURE, characterized by comprising 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and an ammonium compound chosen from: i) an alkyl trimethylammonium salt of formula R-N + (CH3) 3 X - (I) where R denotes an alkyl group containing 20 to 24 carbon atoms, X - denotes a halide ion, in particular chloride or bromide, or a methosulfate ion; ii) 2. MIXTURE, according to claim 1, characterized in that the ammonium compound is the alkyl trimethylammonium salt of formula (I). 3. MIXTURE, according to claim 2, characterized in that, for the trimethylammonium salt of formula (I), R is a behenylene group. MIXTURE according to any one of claims 2 to 3, characterized in that the alkyl trimethylammonium (I) salt is behenyl trimethylammonium chloride. MIXTURE according to any one of claims 2 to 4, characterized in that it comprises 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and the alkyl trimethylammonium salt of formula (I) in quantities so that the weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / salt (I) is in the range of 0.08 to 80, preferably 0.45 to 70 and, preferably, 1.5 to 50. MIXTURE according to any one of claims 2 to 4, characterized in that it has a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / alkyl trimethylammonium (I) salt range from 10 to 60, preferably in the range from 10 to 55, preferably in the range from 15 to 40 and, more preferably, in the range from 20 to 30. MIXTURE according to any one of claims 2 to 4, characterized by having a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / alkyl trimethylammonium (I) salt 0.08 to 5, preferably in the range of 0.45 to 4.5, preferably in the range of 0.45 to 3 and, more preferably, in the range of 1.5 to 3. MIXTURE according to any one of claims 2 to 4, characterized in that it has a weight ratio of 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / alkyl trimethylammonium (I) salt range of 3 to 80, preferably in the range of 3 to 70 and, preferably, in the range of 3 to 50. 9. MIXTURE, according to claim 1, characterized in that the ammonium compound is the alkyldimethylbenzylammonium salt of formula (II). MIXTURE according to claim 9, characterized in that, for the alkyldimethylbenzylammonium salt of formula (II), R is an alkyl group comprising 10 to 16 carbon atoms and preferably 12 to 14 carbon atoms carbon. MIXTURE according to any one of claims 9 to 10, characterized in that the alkyldimethylbenzylammonium (II) salt is an alkyldimethylbenzylammonium chloride. MIXTURE according to any one of claims 9 to 11, characterized in that the alkyldimethylbenzylammonium (II) salt is a mixture of lauryldimethylbenzylammonium chloride and myristyldimethylbenzylammonium chloride. 13. MIXTURE, according to claim 12, characterized in that the alkyldimethylbenzylammonium (II) salt is chosen from the following mixtures: a) a mixture comprising from 60 mol% to 80 mol% of lauryl dimethylbenzylammonium chloride and 20% mol to 40 mol% of myristyldimethylbenzylammonium chloride b) a mixture comprising 65 mol% to 75 mol% of lauryl dimethylbenzylammonium chloride and 25 mol% to 35 mol% myristyldimethylbenzylammonium chloride c) a mixture that comprises from 68% by mol to 72% by mol of lauryl dimethylbenzylammonium chloride and 28% by mol to 32% mol by myristyldimethylbenzylammonium chloride d) a mixture comprising 70% by mol of lauryl dimethylbenzylammonium chloride and 30% by mol of chloride of myristyldimethylbenzylammonium. MIXTURE according to any one of claims 9 to 13, characterized in that it comprises 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one and the alkyldimethylbenzylammonium salt of formula (II) in quantities so that the 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one / salt (II) weight ratio is in the range of 5 to 120, preferably in the range of 5 to 100, preferably in the range of 5 to 85 and, more preferably, from 30 to 85. 15. COMPOSITION, characterized by comprising, in a physiologically acceptable medium, an antimicrobial mixture, as defined in any one of claims 1 to 14. 16. COMPOSITION according to claim 15, characterized in that it comprises at least one additional ingredient chosen from water, oils, polyols containing from 2 to 10 carbon atoms, gelling agents, surfactants, film-forming polymers, dyes, fragrances , fillers, UV protective agents, plant extracts, active cosmetic and dermatological agents and salts. 17. COMPOSITION according to any one of claims 15 to 16, characterized in that 4- (3-ethoxy-4-hydroxyphenyl) butan-2-one is present in a content ranging from 0.01% to 5 % by weight relative to the total weight of the composition, preferably in the range of 0.01% to 3% by weight and, preferably, in the range of 0.01% to 2.5% by weight. 18. COSMETIC TREATMENT PROCESS not therapeutic for the care and / or makeup and / or cleaning of keratin materials, characterized by comprising the application to said keratin materials of a composition, as defined in any one of claims 15 to 17. 19. PROCESS FOR CONSERVING A COMPOSITION comprising a physiologically acceptable medium, in particular, a cosmetic or dermatological cup, characterized in that it consists of incorporating in said composition an antimicrobial mixture, as defined in any one of claims 1 to 14. 20. USE OF AN ANTIMICROBIAL MIXTURE, as defined in any one of claims 1 to 14, characterized in that it is for the conservation of a composition that comprises a physiologically acceptable medium.